The immediate goals of this Center proposal are to (1) foster clinical basic research aimed at the identification of patients with chronic fatigue syndrome, (2) participate in cooperative studies of CFS patients to identify abnormal physiological processes, (3) examine possible genetic mechanisms responsible for the apparent distribution of the syndrome, and (4) apply knowledge of the abnormal physiological processes to identify underlying pathogenesis, "a final common pathway." The central hypotheses are that the physiological processes causing the symptoms of CFS can be measured and compared with better recognized illness processes providing either unique markers of CFS or a pattern of responses that will allow recognition of CFS patients. In addition, the apparent high incidence of allergic diseases in CFS patients provide clues toward understanding the limited distribution of the syndrome and underlying pathogenetic mechanisms. To this end, the Center will perform three sets of measurements on CFS patients identified by strict clinical parameters used in the ongoing Centers for Disease Control Surveillance Study. Neurophysiological measurements of circadian rhythm (heart rate, temperature, sleep, plasma cortisol levels, etc.) autonomic nervous system function, and sleep electrophysiology will be compared with neuropsychiatric measurements of cognitive function, psychiatric parameters and muscle fatigability. Neurophysiological, neuropsychiatric, and fatigue measurements will be performed in matched control groups including healthy persons, persons with allergy, rheumatoid arthritis and major affective disorders (depression). The neuropsychiatric instruments will assess presence or absence of recognized psychiatric disease symptomatology and cognitive functioning. Estimates of muscle fatigability using an isokinetic exercise apparatus and a bicycle ergometer will be performed and compared to subjects' perceived effort. Intrasubject, intragroup and intergroup comparisons of these measurements will be performed to determine possible markers of CFS. Because of the high allergy incidence in CFS patients, CFS patients and allergic controls will be evaluated for expression of cell markers (Eg., CD23) associated with production of mediators of inflammation (IL-1beta TNF-alpha, IL-6 and IL-1 antagonists). The mediators will be quantitational in each subject group to determine if accurate by actual by allergy may be underlying an activated immune system.